The field of this invention pertains to calcium phosphate minerals for bone cement or bone filler applications and in the preparation of such cement. More specifically, this invention relates to a calcium phosphate bone cement comprising a mixture of tetra-calcium phosphate and di-calcium phosphate in an aqueous solution, in which the mixture then sets to form a bone cement with a substantial portion of the cement being hydroxyapatite.
Hydroxyapatite is the major natural building block of bone and teeth. It has been found that bone cements, which are formed by combining calcium and phosphate precursors in an aqueous solution, which initially forms a paste but then hardens into a hydroxyapatite bone cement, are useful in fixing fractures and bone defects. Hydroxyapatite has a calcium to phosphorous ratio of approximately 1.67 which is generally the same as the calcium phosphate ratio in natural bone structures.
These pastes may be placed in situ prior to setting in situations where bone has been broken, destroyed, degraded, become too brittle or has been the subject of other deteriorating effects. Numerous calcium phosphate bone cements have been proposed such as those taught by Brown and Chow in U.S. Reissue Pat. 33,161 and 33,221, Chow and Takagi in U.S. Pat. No. 5,522,893, and by Constantz in U.S. Pat. Nos. 4,880,610 and 5,047,031.
It has been well known since the initial use of calcium phosphate cements that the addition of sodium phosphate solutions, potassium phosphate solutions or sodium carbonate solutions to the aqueous setting solution of the calcium phosphate precursors can speed setting times. This is documented in the Chow et al., April, 1991 IADR Abstract No.: 2410 and AADR, 1992 Abstract No.: 666 and was known to those skilled in the art prior to these publications.
Typically, the powder components, which may be a combination of tetra-calcium phosphate and di-calcium phosphate is supplied in a sterile form in a blister pack or a bottle, e.g., with contents of 2 to 50 g. The liquid, e.g. a molar sodium phosphate solution, distilled water or sodium chloride solution is usually present in a sterile, glass container, usually a disposable syringe, having a volume of 10 cc. The powder and liquid components are usually mixed in a vessel, and processed from this vessel, e.g., by means of a syringe or the like.
It is important that these components of bone cements have long-term stability during storage as these components may be stored for weeks or months before usage when the powder component is mixed with the aqueous component to form a settable material. But, the long-term stability of these components have not been extensively studied because it has been assumed by those skilled in the art that they stay stable with little or no change in properties.
However, unlike the industry's general assumption, according to Uwe Gbureck et al. in Factors Influencing Calcium Phosphate Cement Shelf-life, Biomaterials, (Elsevier Ltd. 2004), it has been found that some prior art powder mixtures of calcium phosphate lose their ability to set after only 7 days of storage, despite being stored in sealed containers. The deterioration of the prior art powder mixtures was subsequently found to be related to their conversion to monetite in a dry state during aging.
Thus, there is a need to develop a rapid setting bone cement which overcomes the destabilization problems of the prior art.
Furthermore, there is also a need to develop an injectable and rapid setting bone cement which can be used in a minimally invasive manner. Minimally invasive surgery is often performed through natural body openings or small “keyhole” incisions, sometimes no more than a quarter-inch in length. When working through such a small opening, it is often desired or required to use a bone cement which can be injected by means of a syringe, for example, into the fractured area.
The commercially available injectable cements currently available in the market, such as Synthes Norian SRS®, Synthes Norian CRS® and Wright Medical MIG X3®, are formulated so that they are readily injectable. However, they have longer setting times, forcing the surgeon to wait as the cements set, prolonging the surgery time.
Some other commercially available bone cement products, such as Synthes Fast Set Putty®, Lorenz Mimix® are rapid setting, but are not readily injectable through a syringe or a needle, rendering the product useless for minimally invasive applications.
Therefore, there is also a continued need to develop a rapid setting bone cement with long-term stability, and also is readily injectable, providing a surgeon with optimal working time and a decreased overall set-time during a minimally invasive surgery.
The invention that is described herein fulfills all of the shortcomings of the currently available commercial products described above.